Sarcoma growth factor (SGF) is an epidermal growth factor (EGF)-like peptide released by murine sarcoma virus (MSV)-transformed cells. It is one of several well-conserved, EGF-like growth factors (GFs) that are released by transformed cells, including a human melanoma line. Any member of this class of GFs, including EGF, can act synergistically with a modulator molecule released by these transformed cells to reversibly induce the transformed phenotype in untransformed indicator cells. This phenotypic transformation is measured as the stimulation of anchorage-independent growth (AIG) of an untransformed cell line; stimulation of AIG is determined using a soft agar colony formation assay. The GF and the modulator have been purified from a Bio-Gel P-60 preparation of crude SGF. The growth factor is EGF-like and is defined as SGF, while the modulator, which has little or no measurable activity when added to these cells in the absence of one of the GFs, appears to be closely related to the TGF-beta reported in the literature. In the AIG assay, EGF can substitute for the GFs released by transformed cells. Antibodies to the EGF receptor block the mitogenic effect of EGF as well as that of SGF. The kinetics of the inhibition are similar for EGF and SGF using antisera from three separate rabbits. The same antisera are able to block the AIG response of a mixture of SGF and modulator, indicating that the occupancy of the EGF receptor by an EGF-like peptide is a requirement for AIG in this system. Synthetic peptides containing portions of the primary structure analogous to SGF have been obtained for the purpose of producing antibodies to the SGF molecule.